Roles of MicroRNAs in Atherosclerosis and Neointimal Lesion Formation under Flow

Abstract

Atherosclerosis, a vascular pathology responsible for most cardiovascular‐related morbidity and mortality, develops predictably in regions of the arterial tree in which wall shear stresses are generated by complex patterns of blood flow. It has been recognized that hemodynamic characteristics determine the location of lesions and contribute to the pathogenesis of atherosclerosis. The key cells involved in atherogenesis include vascular endothelial cells (ECs) and smooth muscle cells (SMCs). Recent evidence suggests that laminar blood flow in the straight part of the arterial tree and high shear stress modulate cellular signaling and EC function, and protect against atherogenesis. In contrast, disturbed flow in bifurcations of the arterial tree and the associated oscillatory low shear stress enhance leukocyte infiltration of the arterial wall and thus are atherogenic. However, little is known about the effect of disturbed flow on ECs, especially on their interactions with SMCs, whose phenotypic switching is significantly implicated in atherosclerosis and neointimal lesion formation. Our recent studies using microRNA (miR) assay, in vitro EC‐SMC co‐culture flow system, experimental animal models, and human specimens from patients with coronary artery disease (CAD) have identified several miRs to be involved in the formation and progression of atherosclerosis. Among these miRs, miR‐146a and 10a play atheroprotective roles in ECs against atherogenesis induced by disturbed flow. MiR‐451, by targeting Rab5a, inhibits vascular SMC proliferation and inflammation and suppresses injury‐induced neointimal lesion formation. Our findings help the discovery of new target biomarkers and elucidation of functional mechanisms underlying atherosclerosis, thereby facilitating the development of new approaches for therapeutic interventions.Support or Funding InformationThis work was supported by grants from the Ministry of Science and Technology in Taiwan (grant numbers: MOST‐106‐2633‐B‐009‐001, 105‐2321‐B‐400‐007, 106‐3114‐Y‐043‐021)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.